6,531 research outputs found
Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs
Non-conding RNAs play a key role in the post-transcriptional regulation of
mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact
with their target RNAs through protein-mediated, sequence-specific binding,
giving rise to extended and highly heterogeneous miRNA-RNA interaction
networks. Within such networks, competition to bind miRNAs can generate an
effective positive coupling between their targets. Competing endogenous RNAs
(ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk.
Albeit potentially weak, ceRNA interactions can occur both dynamically,
affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA
networks as a whole can be implicated in the composition of the cell's
proteome. Many features of ceRNA interactions, including the conditions under
which they become significant, can be unraveled by mathematical and in silico
models. We review the understanding of the ceRNA effect obtained within such
frameworks, focusing on the methods employed to quantify it, its role in the
processing of gene expression noise, and how network topology can determine its
reach.Comment: review article, 29 pages, 7 figure
Measurement of the muon anti-neutrino double-differential cross section for quasi-elastic scattering on hydrocarbon at~ GeV
We present double-differential measurements of anti-neutrino quasi-elastic
scattering in the MINERvA detector. This study improves on a previous single
differential measurement by using updated reconstruction algorithms and
interaction models, and provides a complete description of observed muon
kinematics in the form of a double-differential cross section with respect to
muon transverse and longitudinal momentum. We include in our signal definition
zero-meson final states arising from multi-nucleon interactions and from
resonant pion production followed by pion absorption in the primary nucleus. We
find that model agreement is considerably improved by a model tuned to MINERvA
inclusive neutrino scattering data that incorporates nuclear effects such as
weak nuclear screening and two-particle, two-hole enhancements.Comment: 47 pages, 31 figure
Superconducting imprint of magnetic textures in ferromagnets with perpendicular magnetic anisotropy
Measurement of Total and Differential Cross Sections of Neutrino and Antineutrino Coherent Production on Carbon
Neutrino induced coherent charged pion production on nuclei,
, is a rare inelastic interaction in
which the four-momentum squared transfered to the nucleus is nearly zero,
leaving it intact. We identify such events in the scintillator of MINERvA by
reconstructing |t| from the final state pion and muon momenta and by removing
events with evidence of energetic nuclear recoil or production of other final
state particles. We measure the total neutrino and antineutrino cross sections
as a function of neutrino energy between 2 and 20 GeV and measure flux
integrated differential cross sections as a function of , and
. The dependence and equality of the neutrino and
anti-neutrino cross-sections at finite provide a confirmation of Adler's
PCAC hypothesis
MicroRNAs in cardiac arrhythmia: DNA sequence variation of MiR-1 and MiR-133A in long QT syndrome.
Long QT syndrome (LQTS) is a genetic cardiac condition associated with prolonged ventricular repolarization, primarily a result of perturbations in cardiac ion channels, which predisposes individuals to life-threatening arrhythmias. Using DNA screening and sequencing methods, over 700 different LQTS-causing mutations have been identified in 13 genes worldwide. Despite this, the genetic cause of 30-50% of LQTS is presently unknown. MicroRNAs (miRNAs) are small (∼ 22 nucleotides) noncoding RNAs which post-transcriptionally regulate gene expression by binding complementary sequences within messenger RNAs (mRNAs). The human genome encodes over 1800 miRNAs, which target about 60% of human genes. Consequently, miRNAs are likely to regulate many complex processes in the body, indeed aberrant expression of various miRNA species has been implicated in numerous disease states, including cardiovascular diseases. MiR-1 and MiR-133A are the most abundant miRNAs in the heart and have both been reported to regulate cardiac ion channels. We hypothesized that, as a consequence of their role in regulating cardiac ion channels, genetic variation in the genes which encode MiR-1 and MiR-133A might explain some cases of LQTS. Four miRNA genes (miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2), which encode MiR-1 and MiR-133A, were sequenced in 125 LQTS probands. No genetic variants were identified in miR-1-1 or miR-133a-1; but in miR-1-2 we identified a single substitution (n.100A> G) and in miR-133a-2 we identified two substitutions (n.-19G> A and n.98C> T). None of the variants affect the mature miRNA products. Our findings indicate that sequence variants of miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2 are not a cause of LQTS in this cohort
Epilepsy and neuropsychiatric comorbidities in mice carrying a recurrent Dravet syndrome SCN1A missense mutation
Dravet Syndrome (DS) is an encephalopathy with epilepsy associated with multiple neuropsychiatric comorbidities. In up to 90% of cases, it is caused by functional happloinsufficiency of the SCN1A gene, which encodes the alpha subunit of a voltage-dependent sodium channel (Nav1.1). Preclinical development of new targeted therapies requires accessible animal models which recapitulate the disease at the genetic and clinical levels. Here we describe that a C57BL/6 J knock-in mouse strain carrying a heterozygous, clinically relevant SCN1A mutation (A1783V) presents a full spectrum of DS manifestations. This includes 70% mortality rate during the first 8 weeks of age, reduced threshold for heat-induced seizures (4.7 °C lower compared with control littermates), cognitive impairment, motor disturbances, anxiety, hyperactive behavior and defects in the interaction with the environment. In contrast, sociability was relatively preserved. Electrophysiological studies showed spontaneous interictal epileptiform discharges, which increased in a temperature-dependent manner. Seizures were multifocal, with different origins within and across individuals. They showed intra/inter-hemispheric propagation and often resulted in generalized tonic-clonic seizures. 18F-labelled flourodeoxyglucose positron emission tomography (FDG-PET) revealed a global increase in glucose uptake in the brain of Scn1aWT/A1783V mice. We conclude that the Scn1aWT/A1783V model is a robust research platform for the evaluation of new therapies against DS
Nitrate and nitrite in drinking water affect antioxidant enzymes in erythrocytes of rats
The present study evaluated the effect of short term intake of nitrite and nitrate drinking water on the antioxidant system and membrane damage of rat erythrocytes. Wistar rats were randomly divided into three groups as follows; the group I received only distilled water ad libitum; the group II was given water with nitrate (a dose of 124 mg/kg of nitrate-nitrogen) as drinking water and the group III was given nitrites dissolved in distilled water in a dose of 150 mg/kg for 7 days. At the end of the study, group III rats showed a significant decrease in activities of glutathione peroxidase (GPx), glucose 6-phosphate dehydrogenase (G6PDH) and catalase (CAT), while in group II rats, the activity of GPx and CAT were significantly reduced, but no significant changes in glutathione reductase activity and peroxynitrite levels were observed. On the other hand, malondialdehyde (MDA) was increased in both groups with respect to group I. Also, our major results indicate that all treatments changed methemoglobin levels and osmotic fragility in comparison to group I rats. The intensity of alterations was found more severe in rats of group III, followed by rats of group II. It can be concluded from these observations that nitrate or nitrite leads to alterations in the erythrocytes antioxidant defense status mainly throughout NADPH relate enzymes
ACRATA: a novel electron transfer domain associated to apoptosis and cancer
BACKGROUND: Recently, several members of a vertebrate protein family containing a six trans-membrane (6TM) domain and involved in apoptosis and cancer (e.g. STEAP, STAMP1, TSAP6), have been identified in Golgi and cytoplasmic membranes. The exact function of these proteins remains unknown. METHODS: We related this 6TM domain to distant protein families using intermediate sequences and methods of iterative profile sequence similarity search. RESULTS: Here we show for the first time that this 6TM domain is homolog to the 6TM heme binding domain of both the NADPH oxidase (Nox) family and the YedZ family of bacterial oxidoreductases. CONCLUSIONS: This finding gives novel insights about the existence of a previously undetected electron transfer system involved in apoptosis and cancer, and suggests further steps in the experimental characterization of these evolutionarily related families
Multi-particle azimuthal correlations in p-Pb and Pb-Pb collisions at the CERN Large Hadron Collider
Measurements of multi-particle azimuthal correlations (cumulants) for charged
particles in p-Pb and Pb-Pb collisions are presented. They help address the
question of whether there is evidence for global, flow-like, azimuthal
correlations in the p-Pb system. Comparisons are made to measurements from the
larger Pb-Pb system, where such evidence is established. In particular, the
second harmonic two-particle cumulants are found to decrease with multiplicity,
characteristic of a dominance of few-particle correlations in p-Pb collisions.
However, when a gap is placed to suppress such correlations,
the two-particle cumulants begin to rise at high-multiplicity, indicating the
presence of global azimuthal correlations. The Pb-Pb values are higher than the
p-Pb values at similar multiplicities. In both systems, the second harmonic
four-particle cumulants exhibit a transition from positive to negative values
when the multiplicity increases. The negative values allow for a measurement of
to be made, which is found to be higher in Pb-Pb collisions at
similar multiplicities. The second harmonic six-particle cumulants are also
found to be higher in Pb-Pb collisions. In Pb-Pb collisions, we generally find
which is indicative of a Bessel-Gaussian
function for the distribution. For very high-multiplicity Pb-Pb
collisions, we observe that the four- and six-particle cumulants become
consistent with 0. Finally, third harmonic two-particle cumulants in p-Pb and
Pb-Pb are measured. These are found to be similar for overlapping
multiplicities, when a gap is placed.Comment: 25 pages, 11 captioned figures, 3 tables, authors from page 20,
published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/87
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